The value of the laboratory rodent in biomedical research is compromised by the uncontrollable and poorly understood influence which its intestinal microflora exerts on function and metabolism. Elimination of the undefined microflora is the first and essential step toward full control and definition of the animal model. But germfree studies have revealed a remaining variablity due to dietary influences, as well as a broad spectrum of functional parameters affected by the germfree state itself. This Program Project therefore aims at the development and function description of the nutritionally defined gnotobiote in order to study its patterns of systemic function and metabolism and their interrelations with intestinal microorganisms, and thereby develop an animal tailored to the critical investigation of major health problems. Emphasis will be on development of chemically defined, low molecular weight diets suitable for all phases of life of the germfree rodent, and the determination of quantitative requirements for major nutrients; study of function and metabolism of the defined germfree rodents; and the influence of conventional and defined microfloras on nutrition, function and metabolism. Attention will be given to serological and immunological parameters for the purpose of describing immune functions under controlled conditions. Special microfloras will be developed for the defined gnotobiote in order to bring its parameters of function and metabolism back within conventional range. Other defined stable microfloras resembling those found under conditions of protein-caloric malnutrition and senescence will be tested for their effects on function and metabolism. In this way the Program Project endeavours to develop and describe a defined animal model that can be approximated in a controlled manner to almost any experimental demand. Since not all these demands can be successfully met by the qnotobiotic rat and mouse, the knowledge gained in this project will be used to facilitate the development of the germfree hamster and the germfree gerbil.